Our plans in this revised application for the Center for Neuroscience in Schizophrenia (CNS) represent a natural outgrowth of the collaborative interactions that exist within the large community of basic and clinical neuroscientists on campus. Given the heterogeneity of the schizophrenic syndrome and the lack of consensus regarding its pathogenesis, we believe that a diverse and multidisciplinary approach is the most appropriate conceptual perspective for relating neuroscience and schizophrenia. Consequently, the scientific areas of basic and clinical investigations proposed in this application deliberately include a wide range of topics and approaches to the study of brain function in animal and human subjects. The Center will consist of the Clinical Core; and four major research programs. The Clinical Core will undertake the recruitment, clinical assessment, management, maintenance, and follow-up of clinical and normal subjects required for current and future studies, including those associated with the Seed Money Program. It will, in addition, conduct neuropsychological, autoimmune, sleep, cognitive, and treatment investigations. The four key research programs proposed encompass neurophysiological studies of the alterations in the network properties of hippocampal neurons in rats, neuronanatomical studies of the prefrontal cortex in monkeys , neurophysiological studies of dopaminergic neurons and neurochemical studies of dopamine release in rat forebrain and clinical in vivo NMR assessment of structural and metabolic changes in the brains of schizophrenic patients. As might be expected, certain common themes run through the four programs. For example, a role for frontal cortical dysfunctions in the etiology of schizophrenia is presumed in Programs 2, 3, and 4 and the biological actions of typical and atypical neuroleptics are relevant to all four programs. Our greatest hope and reason for investment in this venture is in the participatory scientific and mutual educational activities between basic neuroscientists and clinical investigators that we see in a Center of this kind, and the emergence from such productive collaborative interactions of new hypotheses and modes for approaching these issues of joint concern, as well as the development of the next generations of investigators who will be sufficiently will trained and equipped to develop successful links between basic and clinical neuroscience relevant to major mental disorders.